The present invention relates generally to novel therapeutic compositions comprising carbohydrate blends and to methods of using the foregoing for the treatment of premenstrual syndrome (PMS).
Each month, for a few days prior to the onset of menstruation, many millions of otherwise-healthy American women develop symptoms of disturbed mood and appetite that can be strikingly similar to those reported by patients with Seasonal Affective Disorder (SAD), carbohydrate-craving obesity, or the non-anorexia variants of bulimia. This syndrome was first termed xe2x80x9cpremenstrual tensionxe2x80x9d by R. T. Frank in 1931 and is a very common phenomenon. According to Guy Abraham of UCLS, xe2x80x9c. . . of every ten patients to walk into a gynecologist""s office, three or four will suffer from premenstrual tension . . . xe2x80x9d, and in some the symptoms will be of such severity as to include attempts at suicide. Current Progress in Obstetrics and Gynecology, 3:5-39 (1980).
Initial descriptions of the Premenstrual Syndrome (PMS) focused on its association with xe2x80x9cnervous tensionxe2x80x9d, headache and weight gain The weight gain observed initially was attributed to excessive retention of salt and water, which does indeed occur in some PMS patients. However, it soon became evident that it was also a consequence of the widespread tendency of PMS individuals to crave and over-consume carbohydrates, particularly foods with a sweet taste. PMS is also now referred to as late luteal phase syndrome. D.N.S. III, Revised, American Psychiatric Association (1987).
There have been numerous suggestions made about the etiology of PMS. For example, some hypothesized that it was caused by a uterine toxin. Others suggested its cause to be over-consumption of sweets, which presumably is followed by excessive insulin secretion, hypoglycemia, and inadequate brain glucose and results in the oft observed depression and anxiety. It also has been postulated that the behavioral symptoms result from tissue edema and that the psychological changes result from feelings of loss or the social complexities generated by the discomforts of menstruation.
However, none of these theories has been substantiated. PMS can persist after hysterectomy and, hence, uterine toxins cannot be its cause. The hyperinsulinism of PMS is not associated with low blood glucose levels, and is probably the consequence of a behavioral aberration (i.e., the tendency of premenstrual women to choose high-carbohydrate diets, which potentiate insulin secretion) rather than the cause. The mood and appetitive changes of PMS are poorly correlated with the tissue swelling; and subhuman primates who are presumably exempt from the psychodynamic or social complexities of human life, also exhibit characteristic behavioral changes premenstrually.
There have been many treatments suggested for overcoming or reducing the symptoms of PMS. Many of these are pharmaceuticals such as vitamin supplements, ovarian hormones, detoxifying agents, and diuretics. Other, non-pharmaceutical treatments include carbohydrate-free diets and irradiation of the ovaries and pituitary. These approaches all have had limited success, however. Currently there is no means of treating the mood and appetite disturbances commonly experienced on a recurring basis by a large number of women. Such a treatment would be of great benefit. The present invention is directed to addressing these, as well as other, important needs.
Serotonin disturbance and/or deficiency is emerging as a leading theory behind the symptoms of PMS. A number of studies have shown that women with PMS have lower serotonin levels than women without PMS.
In mammals, the animal acid tryptophan is the precursor to serotonin synthesis in the brain. Certain carbohydrates when ingested can increase the ratio of tryptophan to large neutral amino acids (T:LNAA) in the blood stream. This increase of T:LNAA allows a higher level of tryptophan to enter the brain, which is necessary for increasing serotonin synthesis. While carbohydrates from normal food can shift this T:LNAA ratio to a limited extent, these normal foods also contain fats and other fibers, both of which slow down digestion and otherwise interfere with the necessary shift in the balance of amino acids in the blood. This invention provides novel carbohydrate blends comprising simple carbohydrates that are rapidly digested and thereby provide relief from the symptoms of PMS, much faster than relief from xe2x80x9cnormal foodxe2x80x9d.
The present invention is directed generally to novel therapeutic compositions comprising rapidly-digestible carbohydrate blends, and to methods of using same for the treatment, prevention, amelioration, or dietary management of PMS. Administration of a composition according to the method of the present invention is of great benefit to women who experience disturbances of mood and/or appetite prior to onset of their menstrual period, as the composition, by supplying particular nutrients for the dietary management of PMS, acts to alleviate and/or prevent such adverse premenstrual symptoms.
Specifically, in one embodiment, the present invention is directed to therapeutic compositions useful for the treatment, prevention or dietary management of PMS, comprising novel blends of carbohydrates, such as, but not limited to, dextrose, galactose, pre-gelatinized starch, mannose, sucrose, maltose, lactose, dextrin, maltodextrin, mixtures thereof, and which are essentially free of and not more than 1-2 grams of fat. Preferably, said therapeutic compositions include carbohydrate blends comprising about 20-100 g of a rapidly-digestible carbohydrate blend in solution essentially free of protein, wherein the solution comprises a ratio of about 3-12 mL water to about total 1 g carbohydrate blend and an acidulant selected from the group consisting of adipic acid, citric acid, fumaric acid, lactic acid, succinic acid, tartaric acid, ascorbic acid, acetic acid, and malic acid, to remain a therapeutically effective pH at less than 6 and wherein the carbohydrate blend comprises about 60-100% dextrose, dextrin, maltodextrin, or a mixture thereof, and 0 to 40% starch or pre-gelatinized starch, or a mixture thereof. More preferable said carbohydrate blends comprise novel mixtures of dextrose and starch, particularly in ratios of about 80% to 100% dextrose to 0 to 20% starch, wherein the total amount of carbohydrate in said blend comprises about 40-80 grams. Still more preferred are compositions comprising carbohydrate blends of dextrose and starch in ratios of about 80% to 85% dextrose to 15 to 20% starch. Specifically preferred is a composition comprising a carbohydrate blend of 45 g dextrose and 3 g starch.
In another embodiment, said carbohydrate blends are in the form of a solution comprising dextrose, starch and water. Preferably, the solution comprises about 2-10 mL of water to 1 gram of carbohydrate blend. More preferably, the solution comprises about 5-6 mL water to 1 gram of carbohydrate blend.
A further embodiment of the invention is directed to compositions wherein the solution further comprises an acidulant to maintain a therapeutically effective pH at less than 6. Such acidulants include, but are not limited to, adipic acid, citric acid, fumaric acid, lactic acid, succinic acid, tartaric acid, ascorbic acid, acetic acid, and malic acid. Preferred are solutions with a pH between about 2 and 5. More preferred is a solution comprising 60 g dextrose and 10 g galactose, 280 mL water and malic acid to maintain the solution at a pH of 2.
Another embodiment of the invention is directed to methods of using said therapeutic compositions for treating, preventing, ameliorating, or managing the effects of PMS. Such methods comprise administering a therapeutically effective amount of said novel compositions to subjects in need of such treatment. Without limiting the invention, and by way of theoretical hypothesis only, it is believed that such therapeutic compositions are effective by increasing the ratio of T:LNAA in the blood stream thereby increasing the level of serotonin production in the brain. Such increase is believed to relieve those PMS conditions related to serotonin and brain functioning by supplying the nutrients necessary for serotonin synthesis.
A further embodiment of the invention is the method of treating, ameliorating, preventing or managing the symptoms of PMS comprising administering a combination of novel carbohydrate blend compositions of the present invention together with other useful agents, such as but not limited to vitamins; tryptophan, tyrosine, and other amino acids; ovarian hormones; detoxifying agents and/or diuretics.
It is also conceivable that novel compositions of present invention could potentially be useful for the treatment of other symptoms and disorders such as appetite control including carbohydrate craving and binge eating; anxiety and depression and smoking disorders in a subject.
The invention describes novel, rapidly-digestible, carbohydrate blend compositions effective to relieve, treat, ameliorate or manage, the symptoms of PMS. The compositions of the present invention comprise 40 to 100% dextrose and 0 to 60% starch, or any other carbohydrate in the carbohydrate blend solution. The more preferred blend is about 80% dextrose and 20% starch. The choice of a particular ratio will depend upon several factors such as the weight of the individual, the rate of effect the carbohydrates have on the subject and the nature and severity of the PMS symptoms or the manner in which the carbohydrate blend is used.
The phrases xe2x80x9ccarbohydrate blendxe2x80x9d or xe2x80x9cblendxe2x80x9d, as used herein and in the claims, refer to mixtures of simple or complex, rapidly-digestible carbohydrates such as, but not limited to, dextrose, galactose, pre-gelatinized starch, mannose, sucrose, maltose, lactose, dextrin, maltodextrin. In a preferred embodiment of the invention, the carbohydrate blend comprises dextrose and starch. The term xe2x80x9cdextrosexe2x80x9d as used herein and in the claims refers to glucose or polymers thereof.
Carbohydrates of the present invention can be obtained from a variety of commercial sources. However, lactose is comprised of 50% dextrose and 50% galactose and galactose is currently only available when lactose is digested. Galactose may be obtained by a process comprising the steps of hydrolysing lactose, crystallizing the products, drying the products and adjusting the ratio of dextrose to galactose by adding anhydrous dextrose. More preferred is the process wherein the hydrolysing step comprises acid or lactase enzymatic hydrolysis. Also more preferred is the process wherein the crystallization step comprises selectively and separately crystallizing the products dextrose and galactose or crystallizing both dextrose and galactose together.
The term xe2x80x9csolutionxe2x80x9d as used herein and in the claims, refers to mixtures of carbohydrate blends in water. The term xe2x80x9cwaterxe2x80x9d, as used herein and in the claims, includes distilled, deionized, or tap water. Preferred is a solution further comprising an acidulant, to maintain a therapeutically effective pH below about 6. The term xe2x80x9cacidulantxe2x80x9d, as used herein, includes acids which can maintain a therapeutically effective pH of the solution. Such acids include but are not limited to adipic acid, citric acid, fumaric acid, lactic acid, succinic acid, tartaric acid, ascorbic acid, acetic acid, and malic acid. Preferred in the acidulant malic acid. The phrase xe2x80x9ctherapeutically effectivexe2x80x9d as used herein and in the claims refers to that amount of carbohydrate blend necessary to administer to a subject to induce the desired effect of treating, ameliorating, relieving, or managing the symptoms of PMS.
Yet another embodiment of the invention is directed to a method of treating PMS comprising the administration such novel compositions. Such method comprises administering said therapeutic composition to an individual, prior to the onset of her menstrual period, in a quantity sufficient to reduce, ameliorate, manage or prevent the mood and/or appetite disturbances, and/or to suppress the weight gain, which otherwise would be observed in the individual prior to onset of menstruation. One or more of the compositions of this invention can be administered for the treatment of PMS by any means that produces contact to the active agent with the agent""s site of action in the body of a mammal. Preferably, the compositions are administered orally. They can be administered by any conventional means available for use in conjunction with therapeutic or dietary agents. They can be administered alone, but generally administered with a carrier selected on the basis of the chosen route of administration and standard therapeutic practice.
The dosage administered will, of course, vary depending upon known factors, such as the pharmacodynamic characteristics of the particular agent and its mode and route of administration; the age, health and weight of the recipient; the nature and extent of the symptoms; the kind of concurrent treatment; the frequency of treatment; and the effect desired. A daily dosage of active ingredient can be expected to be about 20-100 g, with the preferred dose being about 40-60 g.
The length of time during which a therapeutic compositions will be given varies on an individual basis, but will generally begin 1 to 14 days prior to menstruation and may continue for several days (e.g., 3 days) after onset of menstruation.
Dosage forms (compositions suitable for administration contain) from about 20-100 g of active ingredient per unit. In these therapeutic compositions the active ingredient will oridinarily be present in an amount of about 0.5-95% by weight based on the total weight of the composition.
The active ingredient can be administered orally in solid dosage forms, such as capsules, tablets, and powders when taken with a suitable amount of water, or in liquid dosage forms, such as elixirs, syrups, and suspensions so long as the proper ratios of ingredients are maintained. Gelatin capsules contain the active ingredient and other powdered carriers, such as cellulose derivatives, magnesium stearate, stearic acid, and the like. Similar diluents can be used to make compressed tablets. Both tablets and capsules can be manufactured as sustained release products to provide for continuous release of agent over a period of hours. Compressed tablets can be sugar coated or film coated to mask any unpleasant taste and protect the tablet from the atmosphere, or enteric coated for selective disintegration in the gastrointestinal tract.
Further, the therapeutic compositions can also be prepared in the form of a food-stuff. Such forms include but are not limited to: a cold or hot beverage, soup, pudding, wafer, candy, a snack bar, or other snack, etc.
Various colorings and flavorings can be employed in any of the above-mentioned dosage forms to improve the taste of the therapeutic composition to increase patient acceptance, and to make it more palatable. Such flavorings can include but are not limited to artificial or real: chocolate, vanilla, strawberry, coffee, banana, orange, etc.
In these various forms, the compositions can be combined with additional substances, such as those needed to serve as fillers, diluents, binders, flavorings or coloring agents or coating materials.